Alcohol abuse is often associated with acute pancreatitis, but the mechanisms by which ethanol sensitizes or predisposes the pancreas to damage are not clear. Acute pancreatitis is characterized by inflammation and damage to the pancreatic acinar cells. It is generally thought, on the basis of clinical observations and animal studies, that, after an acute episode of pancreatitis, the pancreas regenerates to its full structural and functional capacity within 12-14 days. The pancreas and the liver are developmentally related and both organs express alcohol dehydrogenase and cytochrome P450 2E1. Additionally, alcohol abuse is associated with disease in both organs. It is well established that ethanol consumption impairs liver regeneration. Thus, we speculated that ethanol consumption would also impair pancreatic regeneration. In preliminary studies, using a murine model of alcoholic pancreatitis that combines ethanol feeding and pancreatic damage induced by coxsackievirus infection, we have investigated this possibility. On the basis of histologic and enzymatic data our preliminary results support the suggestion that ethanol feeding impairs pancreas regeneration. It has been shown that regeneration of the pancreas requires the tightly orchestrated, coordinated actions of specific growth factors. It is well documented that ethanol consumption can alter the expression and signaling of growth factors. Therefore, it is our hypothesis that ethanol consumption impairs the ability of the pancreas to regenerate to its full structural and functional capacity after severe damage, and this impairment is mediated by aberrant temporal or quantitative expression of specific growth factors. To test this hypothesis, we propose the following specific aims: 1) To further characterize the ethanol-induced impairment in pancreas regeneration after virally induced pancreatitis 2) To determine the molecular mechanisms responsible for the ethanolinduced impairment in pancreas regeneration. Completion of these specific aims will provide new and important information about the effects of ethanol on pancreatic regeneration, as well as forming the foundation for future studies to determine the molecular and biochemical pathways that are affected by chronic ethanol consumption and result in this ethanol-mediated impairment of regeneration. [unreadable] [unreadable] [unreadable]